Summary Proliferative Vitreoretinopathy (PVR), or growth of scar tissues, is a major cause for the failure of retinal re-attachment surgeries. Many drugs have been proven effective in suppressing PVR;however, there has not been any satisfactory means to deliver them to the retina in a safe manner. Our research in Phase I of this project has shown that airborne nanoparticles are very promising for the delivery of anti-proliferative drugs to the retina;in particular, immediately after vitrectomy, when the eye is filled with gas. Electrospraying and high-frequency ultrasonic nebulization are shown to generate desired particles in 50 - 500 nm range. These airborne particles were delivered to the eye of a pig model and resulted in satisfactory deposition kinetics. Based on the above particle-generation technologies, it is proposed to build an automated turnkey drug nanoparticle generator, which would be ready for use in ophthalmology operating rooms. Proposed Phase II project also covers extensive animal studies to determine the safety and efficacy of certain drugs, when delivered in the form of aerosols. The anti-proliferative drug 5-FU will be tested in combination with low molecular weight heparin. This combination drug will be delivered to PVR models of rabbits, which will be monitored for 10 weeks after the treatment. A PVR grading scale developed at the University of MN will be used to record the effectiveness of the above treatment for different dose levels. Safety of the treatment will be established on the basis of retinal imaging, electroretinography and histopathology. Besides the safety and efficacy study with 5-FU, efficacy of a highly potent drug, Mitomycin C (with or without heparin), will also be examined using the above PVR models. It is anticipated that the proposed treatment would be ready for clinical trials by the end of the Phase II project. This project deals with the treatment of proliferative vitreoretinopathy (PVR), or the growth of scar tissues that cause retinal detachment and hence, the failure of retinal re-attachment surgery. A drug nanoparticle generator would be provided that would enable effective delivery of anti-proliferative agents to the retina. Efficacy and safety studies will be undertaken using a rabbit model of PVR. We expect to be ready for clinical trials by the end of this project.